Inactivation of tumor suppressor genes appears to be the predominant genetic alteration in many solid tumors. In carcinomas inactivation of known tumor suppressor genes includes deletion of one allele and mutation of the remaining allele or homozygous deletion of both alleles (Rodriguez et al. 1994). To date, tumor suppressor genes p53, Rb1, MTS1 and MTS2 were found to be inactivated in a significant proportion of lung carcinomas (Takahashi et al. 1989; Harbour et al. 1988; Shapiro et al. 1995; Washimi et al. 1995). The MTS1 and MTS2 genes seem to be preferentially lost by homozygous deletion on chromosome 9p (Kamb et al. 1994). The p53 tumor suppressor gene on chromosome 17p and the Rb1 tumor suppressor gene on chromosome 13q are frequently inactivated by allelic deletion combined with mutations in the remaining allele (Kishimoto et al. 1992; Hensel et al. 1990). In non-small cell lung cancer (NSCLC), which is the most common type of lung cancer, allelic deletions detected as loss of heterozygosity (LOH) were reported for multiple chromosomal arms (Shiseki et al. 1994; Sato et al. 1994). This indicates inactivation of several tumor suppressor genes in lung tumorigenesis and progression. Generally, overall LOH incidences were higher in squamous cell carcinomas than in adenocarcinomas (Sato et al. 1994). More extensive analyses to determine homozygous and allelic deletions in NSCLC have been performed on chromosomes 3, 5 and 9. This led to the delineation of a minimal region of loss at 9p21, where the MTS1 and MTS2 genes are located (Merlo et al 1994). At least two regions have been identified on chromosomes 3 and 5 to harbor putative tumor suppressor genes involved in lung tumorigenesis (Yokoyama et al. 1992; Ashion-Rickardt et al. 1991; Wieland and Bohm, 1994).
On chromosome 5q allelic deletion of the known tumor suppressor gene APC at 5q21 was frequently observed in advanced NSCLC and it correlated with a poor prognosis (Hosoe et al. 1994; Fong et al. 1995). In squamous cell lung carcinomas LOH at 5q21 also correlates with tumor involvement of regional lymph nodes (Fong et al. 1995). Chromosomal region 5q33-35 is considered another target of frequent allelic deletion in advanced NSCLC (Hosoe et al. 1994). There was recently identified a region on chromosome 5 proximal to the APC gene that harbors the putative tumor suppressor locus del-27 (Wieland and Bohm, 1994). The del-27 sequence was isolated by genomic difference cloning, and it is homozygously deleted in a lung carcinoma cell line (Wieland et al. 1992 GeneBank M99171). Here it is shown by fluorescence in situ hybridization (FISH) that the del-27 locus is on chromosomal region 5p13-12. LOH at the del-27 locus occurred frequently in both, squamous cell and adenocarcinomas of the lung. LOH analysis using five polymorphic microsatellite markers in addition to polymorphic sites at the del-27 and APC loci, clearly identified the del-27 and APC region as two distinct regions with the highest LOH frequencies on chromosome 5.